Remick, DanielStearns-Kurosawa, DeborahZhang, Qiuyang2023-03-062023-03-062022https://hdl.handle.net/2144/45695Sepsis is a syndrome including physiological, pathological and biochemical abnormalities induced by infection. It can lead to multiple organ failure and the kidney is often an early target with severe injury. Sepsis is the most common trigger of acute kidney injury (AKI). Long term AKI often gives rise to chronic kidney injury or kidney failure eventually. AKI is also associated with extremely high mortality. Sepsis induced AKI is strongly associated with poor clinical outcomes. Sepsis induced acute kidney injury (S-AKI) is a rapid decrease in renal excretory function and with accumulation of nitrogen metabolism waste products. The decreasing renal function is due to acute tubular necrosis, which is hard to detect under histological observation. We selected kidney injury molecule 1 (KIM-1) and blood urea nitrogen (BUN) as kidney injury biomarkers to evaluate the damage in the kidney in a murine sepsis model. We also examined a combination of hydrocortisone, ascorbic acid and thiamine (HAT) as treatment for S-AKI. To accomplish this, we stratified the mice to predicted to live (p-live) and predicted to die (p-die) groups based on their heart rate six hours after septic challenge. We performed KIM-1 western blot, enzyme-linked immunosorbent assays (ELISA), hypoxyprobe staining and BUN assay to evaluate the effect and mechanism of HAT therapy on murine S-AKI. Through the experiments, we found the mean of KIM-1 levels increased around 3 times in severe S-AKI mice kidney homogenate samples and plasma samples compared to less injured mice. When we applied HAT therapy to the mice, the mean of KIM-1 level was reduced approximately 2 times compared to the vehicle-treated group. More data should be added to prove the significance. The mean of BUN level increased 2.7 times in the p-die group compared to the p-live, and the mean of BUN concentration also decreased 1.6 times in the HAT treated group than the vehicle treated group. The hypoxyprobe staining showed hypoxic injury primarily in the renal medulla area and HAT therapy significantly reduced the hypoxic injury in the p-die mice. In conclusion, HAT therapy can be a potential effective S-AKI treatment and reduce S-AKI via various mechanisms, including decreased KIM-1 and BUN concentration.en-USPathologyBlood urea nitrogen (BUN)Cecal ligation puncture (CLP)HAT therapy (hydrocortisone ascorbic acid and thiamineKidney injury molecule 1 (KIM-1)SepsisSepsis induced acute kidney injury (S-AKI)Thesis/Dissertation2023-02-23